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Medicine Jun 2024Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal...
Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal relationships between diet-derived circulating antioxidants and 2 non-scarring alopecia using Mendelian randomization (MR). Instrumental variables for antioxidants (lycopene, retinol, ascorbate, β-carotene, α-tocopherol, and γ-tocopherol) were selected from published studies. Data for alopecia areata (AA) and androgenetic alopecia (AGA) was obtained from the FinnGen study project (R9 released in 2023), including 195 cases and 201,019 controls for AGA and 682 cases and 361,140 controls for AA. We used the inverse variance weighted method as the primary MR method. Three additional methods were used as sensitivity analysis to validate the robustness of the results. We found a causal relationship between absolute β-carotene levels and AGA risk (P = .039), but not with AA (P = .283). The results of Wald ratio showed a protective effect of absolute β-carotene levels against AGA, with per 0.1 ln-transformed β-carotene being associated with a 76% lower risk of AGA (OR: 0.24, 95% CI: 0.06-0.93). Based on the fixed effects inverse variance weighting results, we found that α-tocopherol was protective against both AGA (P = .026) and AA (P = .018). For each unit increase in α-tocopherol, the effects of change in AGA and AA were 0.02 (95% CI: 0.00-0.61) and 0.10 (95% CI: 0.01-0.67), respectively. The results did not reveal any other causal relationships. Our study identified 3 causal associations of antioxidants with the risk of non-scarring alopecia. These results provide new insights into the prevention of non-scarring alopecia through diet.
Topics: Humans; Mendelian Randomization Analysis; Antioxidants; beta Carotene; Alopecia; Diet; alpha-Tocopherol; Female; Male; Alopecia Areata; Risk Factors
PubMed: 38875426
DOI: 10.1097/MD.0000000000038426 -
PloS One 2024This study explored the pressing issue of drug and substance abuse (DSA) among adolescents in drug hotspots in Malaysia. The Malaysian Anti-drug Agency (AADK) has...
This study explored the pressing issue of drug and substance abuse (DSA) among adolescents in drug hotspots in Malaysia. The Malaysian Anti-drug Agency (AADK) has identified 155 hotspot areas across Malaysia, of which 78 were randomly selected as the study sites. These areas were identified as having extreme drug-related activities such as drug trafficking and drug-related crimes. According to the literature, several factors influence adolescents to be involved in DSA. Therefore, understanding the risk factors in the context of Malaysian school-going adolescents is of utmost importance. The study examined, in particular, a wide range of potential predictors, including socioeconomic factors, peer influence, family dynamics, educational experiences, drug access, and community characteristics. Adolescents in the hotspot areas were selected by means of a cross-sectional survey design with a cluster sampling method. The sample comprised 3382 school-going adolescents, and the data were collected through face-to-face interviews. The logit model method with STATA software was used to analyse the data. The findings of the study revealed that school-going adolescents with disciplinary issues face a two-fold increase in the risk of becoming current drug users compared to their peers. Further, those exhibiting externalising behaviours, such as aggression and rule-breaking, also face greater odds of becoming involved in DSA. Drug pushers were identified as the most significant risk factor, with adolescents exposed to them being 46 times more likely to become current drug users. The factors of friends and family also contribute significantly to adolescent drug involvement. However, adolescents with academic-related issues may be less involved if they have the protective factor of better coping skills. These findings will contribute to efforts to mitigate drug addiction and drug-related activities, particularly in high-risk communities, as well as help policymakers and healthcare professionals develop targeted interventions and generally promote the well-being of adolescents.
Topics: Humans; Malaysia; Adolescent; Substance-Related Disorders; Male; Female; Cross-Sectional Studies; Risk Factors; Schools; Adolescent Behavior; Drug Trafficking; Socioeconomic Factors
PubMed: 38875293
DOI: 10.1371/journal.pone.0305460 -
Aging Jun 2024Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of...
BACKGROUND
Urological malignancies, including kidney, bladder, and prostate cancer, are major health concerns worldwide. Inflammation has been implicated in the pathogenesis of these cancers, and circulating inflammatory proteins may play a role in their development. However, the causal relationship between specific plasma proteins and urological malignancies remains unclear.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS). Instrumental variables representing genetic variants associated with circulating inflammatory proteins were used to infer causality on the risk of kidney, bladder, and prostate cancer. Four MR methods were utilized to provide robust effect estimates.
RESULTS
Our analysis identified several plasma proteins associated with a lower risk of kidney and bladder cancer, including Eukaryotic translation initiation factor 4E-binding protein 1, Caspase 8, Natural killer cell receptor 2B4, and Tumor necrosis factor ligand superfamily member 12. However, after adjusting for multiple testing, these associations did not remain statistically significant. For prostate cancer, CUB domain-containing protein 1 and Interleukin-10 receptor subunit beta were found to be protective, while Glial cell line-derived neurotrophic factor and SIR2-like protein 2 were identified as risk factors. After FDR adjustment, none of the inflammatory proteins were found to be significantly associated with a lower risk of prostate cancer.
CONCLUSION
Our findings suggest that certain plasma proteins may be involved in the development of urological malignancies. Mendelian randomization provides a useful framework for investigating causal relationships between inflammatory proteins and urological cancers, offering potential insights into their underlying biology and therapeutic targets.
PubMed: 38874503
DOI: 10.18632/aging.205934 -
Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.Clinical Cardiology Jun 2024In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend...
BACKGROUND
In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients.
OBJECTIVES
This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA.
METHODS
We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF.
RESULTS
Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF.
CONCLUSION
Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.
Topics: Humans; Male; Female; Glomerular Filtration Rate; Amyloid Neuropathies, Familial; Aged; Cardiomyopathies; Prognosis; Retrospective Studies; Risk Factors; Middle Aged; Follow-Up Studies; Renal Insufficiency, Chronic; Disease Progression; Kidney; Time Factors; Incidence; Risk Assessment
PubMed: 38873847
DOI: 10.1002/clc.24298 -
Frontiers in Immunology 2024The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common...
BACKGROUND
The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited.
OBJECTIVE
This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections.
METHODS
Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients.
RESULTS
Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order , including the family . Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of and genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of and was associated with acute respiratory infections within six months.
CONCLUSIONS
CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.
Topics: Humans; Common Variable Immunodeficiency; Oropharynx; Male; Female; Middle Aged; Adult; Respiratory Tract Infections; Dysbiosis; Microbiota; Prospective Studies; Aged; RNA, Ribosomal, 16S; Acute Disease; Bacteria; Case-Control Studies
PubMed: 38873612
DOI: 10.3389/fimmu.2024.1371118 -
Frontiers in Immunology 2024Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory...
OBJECTIVES
Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE.
METHODS
We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.
RESULTS
Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05).
CONCLUSIONS
Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Genome-Wide Association Study; Genetic Predisposition to Disease; Mendelian Randomization Analysis; Phenotype; Polymorphism, Single Nucleotide; Biomarkers; Adult; Inflammation
PubMed: 38873604
DOI: 10.3389/fimmu.2024.1389843 -
Food Science & Nutrition Jun 2024Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial....
Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial. Therefore, we have adopted Mendelian randomization (MR) analysis to investigate the causal relationship between different types of meat intake and acne. The exposure and outcome datasets for this study were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS project. Seven datasets on meat intake were included, which consisted of non-oily fish, oily fish, lamb/mutton, poultry, pork, beef, and processed meat. The main methods used for MR analysis were inverse variance weighted, weighted median, and MR-egger. To ensure the accuracy of the results, heterogeneity, pleiotropy, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) analyses were conducted. Additionally, an analysis of four risk factors (fasting insulin, insulin resistance, total testosterone level, and estradiol level) was performed to investigate the underlying mechanisms linking statistically significant meat intake to acne. Oily fish intake was found to be a protective factor for acne (OR: 0.22, 95% CI: 0.10-0.49, < .001), and it was also observed that oily fish intake can reduce the level of fasting insulin by the IVW method (OR: 0.89, 95% CI: 0.81-0.98, = .02). No causal relationship was identified between other types of meat intake and acne. The intake of oily fish reduces the risk of acne by lowering fasting insulin levels.
PubMed: 38873457
DOI: 10.1002/fsn3.4054 -
Frontiers in Pharmacology 2024Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are...
INTRODUCTION
Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients, R. Br and (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism.
METHODS
LHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32 g/kg, 0.64 g/kg, and 1.28 g/kg) of LHT and the positive medication, sulfasalazine (0.2 g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT's impact.
RESULTS
LHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, , , and levels while decreasing and r levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with , , , , and negatively with , , and Patescibacteria. Furthermore, colony network analysis revealed that was negatively associated with and , whereas was positively related to .
CONCLUSION
LHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.
PubMed: 38873425
DOI: 10.3389/fphar.2024.1413666 -
Frontiers in Pharmacology 2024In China, plants are widely used to reduce atopic dermatitis and inflammation-related diseases, but their protective mechanisms remain unclear. This study investigated...
In China, plants are widely used to reduce atopic dermatitis and inflammation-related diseases, but their protective mechanisms remain unclear. This study investigated the anti-allergic dermatitis, anti-oxidation and anti-inflammation effect and underlying mechanism of five species, including , var. , , , and . . A total of about 110 chemical compositions were detected from five teas extracts. The level of mast cell infiltration in the model mice skin was determined by HE (Hematoxylin and eosin) staining and toluidine blue staining, and the level of interleukin-1 (IL-1β) and nerve growth factor was detected by immunohistochemistry. The five Camellia tea leaf extracts have histamine-induced allergic dermatitis. Lipopolysaccharide (Lipopolysaccharide)-induced murine macrophage RAW264.7 inflammation model was found to secrete NF-κB factor, as shown by immunofluorescence, and reactive oxygen species secretion and related cytokine levels were detected. The results suggested that Camellia's five tea extracts had the ability to resist cellular oxidative stress. In addition, the results of cell inflammatory cytokines including fibronectin (FN) and interleukin-6 (IL-6) suggested that the five tea extracts of had anti-inflammatory effects. Therefore, it is suggested that five teas may possess inhibitory properties against allergic reactions, oxidative stress, and inflammation, and may prove beneficial in the treatment of allergies.
PubMed: 38873420
DOI: 10.3389/fphar.2024.1296190 -
Journal of the Korean Society of... May 2024This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications.
PURPOSE
This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications.
MATERIALS AND METHODS
We conducted a retrospective review of 477 lung biopsy CT scans performed during free breathing. The respiratory phases during pleural puncture were determined based on the table position of the targeted nodule using CT scans obtained during free breathing. We compared the rates of complications among the inspiratory, mid-, and expiratory respiratory phases. Logistic regression analysis was performed to control confounding factors associated with pneumothorax.
RESULTS
Among the 477 procedures, pleural puncture was performed during the expiratory phase in 227 (47.6%), during the mid-phase in 108 (22.6%), and during the inspiratory phase in 142 (29.8%). The incidence of pneumothorax was significantly lower in the expiratory puncture group (40/227, 17.6%; = 0.035) and significantly higher in the mid-phase puncture group (31/108, 28.7%; = 0.048). After controlling for confounding factors, expiratory-phase puncture was found to be an independent protective factor against pneumothorax (odds ratio = 0.571; 95% confidence interval = 0.360-0.906; = 0.017).
CONCLUSION
Our findings suggest that pleural puncture during the expiratory phase may reduce the risk of pneumothorax during image guided PTNB.
PubMed: 38873383
DOI: 10.3348/jksr.2023.0093